The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling
Open accessAbstract
Maintenance of adult tissues is carried out by stem cells and is sustained throughout life in a highly ordered manner. Homeostasis within the stem-cell compartment is governed by positive- and negative-feedback regulation of instructive extrinsic and intrinsic signals. ErbB signalling is a prerequisite for maintenance of the intestinal epithelium following injury and tumour formation. As ErbB-family ligands and receptors are highly expressed within the stem-cell niche, we hypothesize that strong endogenous regulators must control the pathway in the stem-cell compartment. Here we show that Lrig1, a negative-feedback regulator of the ErbB receptor family, is highly expressed by intestinal stem cells and controls the size of the intestinal stem-cell niche by regulating the amplitude of growth-factor signalling. Intestinal stem-cell maintenance has so far been attributed to a combination of Wnt and Notch activation and Bmpr inhibition. Our findings reveal ErbB activation as a strong inductive signal for stem-cell proliferation. This has implications for our understanding of ErbB signalling in tissue development and maintenance and the progression of malignant disease.
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Statistical significance for genomewide studies
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Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
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Self-citationIdentification of stem cells in small intestine and colon by marker gene Lgr5
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Self-citationPaneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Sato, T., van Es, J. H., Snippert, H. J., Stange, D. E., Vries, R. G., van den Born, M., Barker, N., Shroyer, N. F., van de Wetering, M., & Clevers, H. (2011) · Nature · doi:10.1038/nature09637 · Cited by 2,510
Coexistence of Quiescent and Active Adult Stem Cells in Mammals
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Self-citationLgr5 marks cycling, yet long-lived, hair follicle stem cells
Jaks, V., Barker, N., Kasper, M., van Es, J. H., Snippert, H. J., Clevers, H., & Toftgård, R. (2008) · Nature Genetics · doi:10.1038/ng.239 · Cited by 966
Self-citationInterconversion Between Intestinal Stem Cell Populations in Distinct Niches
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Self-citationThe intestinal epithelial barrier: a therapeutic target?
Odenwald, M. A., & Turner, J. R. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.169 · Cited by 1,288
The intestinal crypt, a prototype stem cell compartment
Clevers, H. (2013) · Cell · doi:10.1016/j.cell.2013.07.004 · Cited by 1,223
Self-citationGrowing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications
Sato, T., & Clevers, H. (2013) · Science · doi:10.1126/science.1234852 · Cited by 1,170
Self-citationThe Lgr5 intestinal stem cell signature: robust expression of proposed quiescent ‘+4’ cell markers
Muñoz, J., Stange, D. E., Schepers, A. G., van de Wetering, M., Koo, B., Itzkovitz, S., Volckmann, R., Kung, K. S., Koster, J., Radulescu, S., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.166 · Cited by 772
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Metadata
- Authors
- Wong, V. W. Y., Stange, D. E., Page, M. E., Buczacki, S., Wabik, A., Itami, S., van de Wetering, M., Poulsom, R., Wright, N. A., Trotter, M. W. B., Watt, F. M., Winton, D. J., Clevers, H., & Jensen, K. B.
- Venue
- Nature Cell Biology
- Published
- 2012-03-04
- Volume
- 14
- Issue
- 4
- Pages
- 401-408
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2061644007
- Cited by
- 410
- References
- 8
- FWCI
- 19.32
- Type
- journal article
- Language
- en
- Open access
- green
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- Wong, V. W. Y., Stange, D. E., Page, M. E., Buczacki, S., Wabik, A., Itami, S., van de Wetering, M., Poulsom, R., Wright, N. A., Trotter, M. W. B., Watt, F. M., Winton, D. J., Clevers, H., & Jensen, K. B. (2012). Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nature Cell Biology. https://doi.org/10.1038/ncb2464
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